The present invention relates to a process for preparing peptoidic, peptidic and chimeric peptide-peptoidic dendrimers by multiple iterative multicomponent reactions (MCRs), especially UGI or PASSERINI multicomponent reactions, to compounds thus obtained and to their use.
Dendrimers are supramolecular, branched architectures of well-defined molecular weight. These molecules branch outwardly from multifunctional core units to form more or less regular three-dimensional shells, the peripheral end groups of which form the surface (cf. FIG. 1). Having a high degree of molecular uniformity, low polydispersity and properties making them attractive materials for the developments in nanomedicine in particular, dendrimers are very interesting in many respects. The high diversity and molecular sizes achievable with this method exceed previously known techniques and their possibilities. Dendrimers show potential for use in targeting, for example, as contrast media, coating, drug display, drug delivery, light-harvesting or energy transfer, and for use in nanobiosystems.
The most common and simple method of constructing dendrimers employs so-called divergent methods of synthesis. This refers to the construction strategy which starts with the core unit and produces the dendrimer in a synthesis “from in to out”. Divergent syntheses are generally simple to do and therefore are employed with preference. Yet there is one immense disadvantage in that complete reactions are often impossible in higher generations due to steric hindrances, resulting in the formation of so-called “mistakes”. The product mixtures obtained are then difficult to purify by chromatography. There are also convergent syntheses, wherein the dendrimers are constructed “from out to in”. Although convergent syntheses are less common than divergent syntheses, this strategy does have certain advantages. The formation of “mistakes” is minimized and the dendrons produced are easier to purify. However, one disadvantage consists in the binding of dendrons to core units, which is frequently unsuccessful owing to steric hindrance.
Divergent and convergent syntheses aside, there are also more recent methods in existence, such as orthogonal synthesis, the convergent two-step method, the doubly exponential method, solid-phase synthesis and also coordination-chemical synthesis.
The syntheses mentioned all have the disadvantage of minimal scope for variation in constructing the dendrimers, since the reagents used, such as acrylonitrile, acrylic esters and dihydroxybenzyl alcohols for example, cannot be modified in their basic structure owing to their chemical reaction characteristics.